Connections in the mammalian central nervous system (CNS) are remarkably precise, as is exemplified in the organization of the vertebrate visual system. The major aim of this proposal is to study how the adult pattern of precise and orderly connections emerges during the prenatal development of the cat's visual system. Two different aspects are being studied. One concerns the normal prenatal development of connections between retina, lateral geniculate nucleus (LGN), and visual cortex: when do these connections form and when are the adult patterns of topography and segregation according to eye input attained? What roles do synaptogenesis and the formation of functional connections play in this process? The other concern is with the prenatal development of visual connections in the Siamese cat. In these animals the visuotopic map contained within the LGN and visual cortex has been systematically altered due to a genetic mutation. The main question to be considered is whether the time course and pattern of development of the retino-geniculo-cortical pathway in Siamese cats are entirely different from those of normal animals. A variety of modern neuroanatomical tracing methods are being used. The development of connections between retina, LGN and cortex is being studied autoradiographically by means of the transneuronal transport of radioactively labeled materials in fetuses of known gestational age receiving a unilateral eye injection of tritiated amino acids. The anterograde transport of radioactively labeled materials and/or the retrograde transport of horseradish peroxidase following localized injections is being used to examine the process by which topographically ordered connections develop. An electron microscopic study of synaptogenesis has been initiated, and the presence of functional connections will be assessed by means of fetal electrophysiology.